Abstract 1506: Inward Rectifier and Transient Inward Currents Contribute to Age-Dependent Changes in β-Adrenergic-Induced Delayed afterdepolarizations and Triggered Activity in Rabbit Coronary Sinus
Ectopic foci in pulmonary veins and coronary sinus (CS) are an important cause of atrial fibrillation. We have previously shown that in the presence of β-agonist CS cells of adult and old rabbits generate delayed afterdepolarizations (DAD) and triggered activity (TA) with higher DAD amplitude and TA incidence in old CS. To assess ionic mechanisms of DAD, major determinants of DAD amplitude - transient inward (Iti) and inward rectifier (IK1) currents were recorded in single cells isolated from CS and left atrial free wall (LA) of adult (3 months) and old (2.5–3 years) rabbits.
Methods: In whole-cell-voltage clamp, oscillatory Iti was induced at different test potentials following conventional conditioning steps (0.33 Hz, 1 s) from −80 to +30 mV. Iti was measured as the difference between the current at the onset of the oscillation and the current at maximum excursion of the oscillation. To record IK1, ramp voltage clamp pulses were applied from a holding potential of −120 to +20 mV at a rate of 47 mV/s.
Results: In control, no detectable Iti was seen in any tissue. Isoproterenol (Iso, 10−8 and 10−6 M) had no effects on LA but induced concentration-dependent increases of Iti in CS cells. There was no difference in Iso-induced Iti between adult and old CS cells (at membrane potential −80 mV and Iso 10−6 M, 2.7±0.7 (n=11) and 2.5±0.5 (n=7) pA/pF, respectively, P>0.05). In control, IK1 was similar in adult LA and CS cells (at −110 mV, −4.45±0.76 (n=5) and −4.61±0.39 (n=9) pA/pF), whereas in old CS cells IK1 was smaller at all membrane potentials (at −110 mV, −2.46±0.34 pA/pF (n=9), P<0.05). As a result, slope conductance at the reversal potential was significantly reduced in old CS (0.07±0.01 vs 0.11±0.01 nS/pF in adult, P<0.01). Iso had no effects on IK1 in any tissue.
Conclusions: In CS cells, β-adrenergic stimulation induces Iti which trigger DAD. Reduced IK1 in aged CS tissue allows greater depolarization for any given Iti and therefore may contribute to age-associated increases of atrial tachyarrhythmias and fibrillation.